EP 237: How genetics and environment shape neurodegeneration in Alzheimer's and Parkinson's with Sarah Marzi of King’s College London

This week on The Genetics Podcast, Patrick is joined by Dr. Sarah Marzi, Senior Lecturer at King's College London and group leader at the UK Dementia Research Institute. They discuss the impact of genes and environment on neurodegenerative disease, including: how APOE genotype shapes microglial function, how cell type-specific epigenomics of postmortem brain tissue is revealing the role of microglia and oligodendrocytes in Alzheimer's disease, and how pesticide exposure drives selective dopaminergic neuron loss and neuroinflammation in Parkinson's.Show Notes0:00 Intro to The Genetics Podcast00:59 Welcome to Sarah02:13 Environmental contributions to Parkinson’s disease and ALS05:01 The role of microglia in Alzheimer’s disease and findings from a study on APOE variants in a mouse model12:50 APOE4 effects on lipid accumulation, microglial activation, and vitamin D receptor signaling 14:20 Building a multi-omic atlas of the Alzheimer’s brain18:01 Overview of the pathological cascade of events in the Alzheimer’s brain20:31 Anti-amyloid therapies, early intervention, and combination treatment strategies 22:24 Rotenone exposure and microglial immune activation in Parkinson’s disease29:24 Dopaminergic neuron vulnerability to pesticide exposure and mitochondrial dysfunction 31:04 Familial Parkinson’s genes, polygenic Alzheimer’s risk, and genetically targeted clinical trials33:13 Polygenic risk and microglial cell state regulation in Alzheimer’s disease34:13 Defining cell states in single cell RNA sequencing35:30 Oligodendrocyte epigenetic and transcriptional changes in Alzheimer’s disease37:23 Sarah’s most memorable hiking adventures38:58 Closing remarksFind out more:Alzheimer’s APOE microglia xenotransplantation studyRotenone exposure Parkinson’s study